Cardiovascular effects of cocaine are being extensively studied using various species of animals as model systems. A recent study has investigated whether the high dose depressant effects of cocaine on cardiovascular function are due to its sodium channel blocking (local anesthetic) properties. In anesthetized rabbits, high doses of cocaine produces decreases in blood pressure and heart rate and disruptions in cardiac conduction. Similar effects are observed following lidocaine administration in equimolar doses, although lidocaine was less potent that cocaine. These results suggest that cocaine's depressant effects are primarily due to its local anesthetic properties, although cocaine may be more potent than lidocaine. These results further suggest that cocaine's adverse effects following repeated administration may be due to its local anesthetic effect, because acute tolerance does not develop to the local anesthetic effects of cocaine. Another recent study has shown that cocaine appears to produce its cardiovascular effects in rats through two distinct mechanisms. Following intravenous administration in rats cocaine produces an initial large, brief increase in blood pressure and heart rate, followed by more prolonged, but smaller increases in blood pressure and heart rate. The prolonged increases in blood pressure and heart rate could be blocked by dopamine antagonists and mimicked by the dopamine-selective uptake inhibitor GBR 12909. The larger initial increase in blood pressure and heart rate was not blocked by the dopamine antagonists, nor mimicked by any monoamine uptake inhibitors. Lidocaine produced no increases in either blood pressure or heart rate. These results suggest that two pharmacodynamic actions of cocaine mediate its cardiovascular effects. The prolonged increases are due to dopaminergic mechanisms, while the initial increases are dependent on neither the monoamine uptake nor local anesthetic properties of cocaine.